Oxidant stress contributes to the pathogenesis of hypoxic-ischemic encephalopathies. Platelet-activating factor (PAF) is generated during oxidant stress. We studied the vasomotor mode of actions of PAF on periventricular (PV) microvessels of fetal (≈75% of term), newborn (1–3 days), and adult pigs. PAF constricted PV microvessels from fetal (29.27 ± 2.6%) and newborn (22.14 ± 3.2%) pigs but was ineffective in adults (<2.5%). Specific [³H]PAF binding was greater in fetus and newborn than in adults; a concordant developmental PAF-induced inositol phosphate formation was observed. PAF-induced vasoconstriction was abrogated by thromboxane A₂(TXA₂) synthase and receptor inhibitors, calcium channel blockers, and by removal of endothelium; vasoconstriction to TXA₂ mimetic U-46619 did not differ with age. Immunoreactive TXA₂ synthase expression and PAF-evoked TXA₂ formation revealed a fetus> newborn>adult profile. Thus the greater PAF-induced PV microvascular constriction in younger subjects seems attributable to greater PAF receptor density and mostly secondary to TXA₂ formation from endothelium. The resulting decrease in blood flow may contribute to the increased vulnerability of the PV brain regions to oxidant stress-induced injury in immature subjects.